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Alert Number 45

Vioxx Warning

Date: October 1, 2004

Unless you have totally cut yourself off from all forms of media, you must have heard the news by now: Merck has withdrawn its multi-billion dollar drug Vioxx from the market. There have been concerns since the publication of the large scale study (VIGOR) in 2001 regarding the potential for increased cardiovascular risk in patients who took Vioxx, as compared to other NSAID drugs such as aspirin in the treatment of arthritis.

Vioxx and Celebrex are promoted as specific COX-2 inhibitors, able to deal with the inflammation pain of arthritis without the usual GI tract ulcers and bleeding associated with long term use of older NSAID drugs, which inhibited both COX-1 and COX-2. Nothing in life is simple. There is still a great deal of controversy regarding the exact mechanism of the higher incidence of cardiac problems seen with Vioxx use. At this point in time, there is no formal finger pointing at Celebrex, the other major COX-2 inhibitor in the market, but that may (or may not!) change with time. If you are in the habit of swallowing large doses of Vioxx as a cancer-control mechanism, you should surely revisit that logic, especially if you are at high risk of cardiac problems to begin with. As for Celebrex, the available information does not draw similar conclusions, at this point.

However, I would like to take this opportunity to make one very simple and well documented point. Many of the cancer drugs that you may need in the future to control your CLL are not exactly heart friendly. Even Avastin, the antibody that blocks VEGF, has been cited for some cardiac toxicity. There will be stress on your cardiac function, from one or several of the drugs that you will need. Think of it as a storm warning. You know it is coming - it is just a matter of time. Does it not make sense to get prepared for it, get your body in fighting trim so that you can better handle the cardiac stresses coming your way? Nothing helps your heart as much as healthy eating, regular exercise, sufficient sleep and stress reduction. And for heaven's sake, quit smoking if you are still doing it!

Be well,



J Hum Hypertens. 2004 Sep 23 [Epub ahead of print]

Cardiovascular risk and COX-2 inhibition in rheumatological practice.

Justice E, Carruthers DM.

Department of Rheumatology, Sandwell and West Birmingham Hospitals Trust, City Hospital, Dudley Road, Birmingham, UK.

The use of specific COX-2 inhibitors in place of standard nonsteroidals for the treatment of arthritis appears to reduce the risk of serious gastrointestinal toxicity in this group of patients. However, the role played by these inhibitors in the generation or exacerbation of ischaemic cardiovascular disease is less clear. Clinical studies demonstrate that hypertension can be induced or aggravated by COX-2 inhibitors to a degree similar to that which occurs with standard nonsteroidals. Endothelial dysfunction, an indicator of cardiac ischaemia, may also be exacerbated by specific COX-2 inhibition and there is much debate as to whether these changes lead to an absolute increase in ischaemic cardiac events. These effects on cardiovascular risk factors appear all the more important in patients with rheumatoid arthritis where there is an increase in the incidence of ischaemic heart disease. Here we review the available data on COX-2 inhibition and cardiovascular disease and conclude that all patients who started these agents should have a careful assessment and modification of any cardiovascular risk factors.Journal of Human Hypertension advance online publication, 23 September 2004; doi:10.1038/sj.jhh.1001777

PMID: 15385947

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